Regulation of midkine messenger ribonucleic acid levels in cultured rat granulosa cells.

To investigate the regulation of ovarian midkine (MK) production at the mRNA level, we evaluated changes in MK mRNA in cultured granulosa cells. The level of MK mRNA increased in a time-dependent manner in the presence of FSH or retinoic acid (RA). FSH increased MK mRNA levels in a dose-dependent manner to a maximum of about 2-fold increase. The stimulatory effects of FSH were mimicked by 8-Br-cAMP. RA increased MK mRNA levels in a dose dependent manner to a maximum of about 2 fold increase at a concentration of 0.3 microM. These results show that granulosa cells produce MK mRNA under the independent control of FSH and RA. The coexistence of FSH and RA in this culture exerted no additive effect on the induction of MK mRNA. Analysis of FSH receptor mRNA induction by both reagents revealed that FSH stimulated expression of the FSH receptor while RA had an inhibitory effect on FSH receptor induction regardless of the presence of FSH. These data show that RA increases MK mRNA, and decreases FSH receptor expression, by a pathway independent of cAMP.